The goal of this project is to develop a novel all-purpose programmable and scalable digital biochip instrument that has unprecedented power and flexibility for microarray and lab-on-a-chip applications. The main approach is to integrate active-matrix driving circuitry into droplet-based microfluidic platform. The first-ever integration of an active-matrix circuitry into microfluidic system brings forth multiple breakthroughs in biochip functionality and usability. Firstly, the biochip is a truly all-purpose bioanalytical and biosynthetic platform. The functionality of the biochip can be changed based on the content inside the droplets. By selectively addressing a subset of electrodes in the array, the biochip can be dynamically reconfigured to suit a specific task by a computer according to pre-designed application protocols. Secondly, the biochip is capable of handling massive parallel reactions at one time. The freedom in droplet actuation through active-matrix circuitry allows parallel manipulation of multiple droplets simultaneously. Active-matrix circuitry can be easily scaled up to contain thousands of rows and columns, thus it is straightforward to process more than a million droplets concurrently. This would provide unprecedented power for addressing large and complex bioanalysis tasks that conventionally deemed prohibitive. Thirdly, unlike current microarray and custom-built lab-on-a-chip device for a specific application, the digital biochip is completely reusable, thus lowering its cost-of- ownership and making it broadly accessible. The development of the prototype digital biochip instrument will be accomplished through four tasks: 1) Design and fabricate a prototype digital biochip with an active-matrix electrode array for droplet manipulation;2) Design and develop a control circuit board for computer-biochip interfacing;3) Develop and implement active-matrix circuitry driving algorithm for droplet manipulation;4) Demonstrate prototype instrument operation in screening for protein crystallization. The successful development and construction of the prototype biochip instrument can be considered as a major advancement in microarray technology and lab-on-a-chip development. It will pave the way for future extension of the prototype instrument into a full- fledged digital biochip instrument that can handle millions of droplets simultaneously. PUBLIC HEALTH RELEVANCE (provided by the applicant): Upon completion, this project will present a novel all-purpose programmable and scalable digital biochip instrument. The instrument has the potential to become a revolutionary tool for biomedical and clinical researchers to carry out array-based bioanalytical and biosynthetic tasks with significantly reduced time, labor and cost. The successful development of the prototype instrument will prove the feasibility of the concept and pave the way for future extension of the prototype instrument into a full-fledged digital biochip instrument that can handle millions of droplets simultaneously. Digital biochips with millions of pixels will provide unprecedented capability, flexibility, simplicity and reusability to biomedical or clinical researchers to carry out a wide-variety of bioanalytical and biosynthetic tasks for biomedical applications. Potential applications include, but are not limited to, genomic and proteomic assays, single cell study, point-of-care clinical diagnostics, toxin and pathogen detection and identification, environmental monitoring, screening for new drugs and fine-chemical synthesis.